Studies on the disorders in learning new information which occupies an important part of the mental activities of human and on the disorders in keeping and recalling already learned information are main themes for elucidating higher brain functions which have been regarded as the final frontier of life science. However, the cause for the disorders is unclear even at present and there are no sufficiently effective medicaments yet, so that early development of therapeutic drugs is greatly demanded. Even in the case of medicaments which have been reported to be effective in improving impairment in learning and memory of dementia patients to a certain degree, it has been pointed out that the duration of action is short and the clinically effective range is narrow (Feldman H. et al., (2001), Neurology, 57 (4), 613–20), that side effects such as hepatic toxicity and the like are generated (Summers W. K. et al., (1989), Lancet, 1 (8640), 729) and the like. In addition, for the purpose of finding an agent showing a useful therapeutic effect, it is necessary to take into consideration not only its in vitro efficacy but also in vivo bioavailability and transferring activity into the brain of the agent itself. Accordingly, the presence of a model animal which can be analyzed at individual level is essential for the elucidation of onset mechanism of the disease, prevention of onset of the disease or improvement of its pathologic condition, development of medicinal techniques for the treatment and of medicaments, and the like.
The transgenic mouse is expected as a method for displaying functions of genes in the living body for development of models for respective human diseases and development of various therapeutic drugs using these models. Including the c-myc oncogene-introduced transgenic mouse as a leukemia model which received a patent for a living life for the first time in the world (U.S. Pat. No. 5,087,571), various pathological model mice have been introduced, such as a prostatic hyperplasia mouse (U.S. Pat. No. 5,175,383), a diabetes mellitus-generating mouse (Japanese Patent 2771493), an Alzheimer'S disease model mouse (Games D. et al., (1995), Nature, 373 (6514), 523–7) and the like. Although many of the dementia-related transgenic animals represented by an APP transgenic show pathologic changes of dementia, it is difficult to detect impairment of learning and memory as a behavioral pattern in these animals, so that attempts have been made detect it by adding some factors such as aging and the like (Moran P. M. et al., (1995), Proc. Natl. Acad. Sci. USA, 92, 5341–5345; Hsiao K. et al., (1996), Science, 274, 99–102; Arendash G. W. et al., (2001), Brain Res., 891, 42–53). However, because preparation of such transgenic animals takes time, it was not practical to conveniently mass-prepare transgenic animals capable of detecting disorders of learning and memory as a behavioral pattern for use in the screening of a substance for antidementia.
Accordingly, demands have been directed toward a model animal to be used as an effective tool for screening a substance for antidementia or a substance to improve learning and memory, and a method for screening a substance for antidementia or a substance to improve learning and memory, which uses said model animal.
On the other hand, anxiety is a physiological phenomenon functioning as a warning against a present or potential danger. Anxiety becomes pathologic when it occurs without a real danger or its emotional strength intensifies. It is known that both of the physiological and pathological anxieties can threaten life when an organ disorder is generated in spite of its previous presence and may cause or permanently keep various physiological dysfunctions. There are various reports on transgenic animals as models of anxiety (Holmes A., (2001), Neurosci. Biobehav. Rev., 25 (3), 261–73). However, there is no applicable and optimum agent having less side effects even now.
Regarding a potassium channel BEC1 which can be used in preparing the transgenic animal of the present invention, the present inventors have disclosed it in WO 99/37677, and there are many reports regarding polynucleotides and polypeptides having a homology of from 98 to 99% with the BEC1 (WO 00/05346, WO 00/09534, WO 99/43696). However, a BEC1 transgenic animal was not prepared in reality, and its functions were not necessarily understood completely.